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However, the treatment of AD remains challenging owning to the hindrance caused by the blood\u2013brain barrier (BBB) and the complex pathology of AD. Nasal delivery represents an effective means of circumventing the BBB and delivering drugs to the brain. In this study, black phosphorus (BP) is used as a drug carrier, as well as an antioxidant, and loaded with a tau aggregation inhibitor, methylene blue (MB), to obtain BP\u2010MB. For intranasal (IN) delivery, a thermosensitive hydrogel is fabricated by cross\u2010linking carboxymethyl chitosan and aldehyde Pluronic F127 (F127\u2010CHO) micelles. The BP\u2010MB nanocomposite is incorporated into the hydrogel to obtain BP\u2010MB@Gel. BP\u2010MB@Gel could be injected intranasally, providing high nasal mucosal retention and controlled drug release. After IN administration, BP\u2010MB is continuously released and delivered to the brain, exerting synergistic therapeutic effects by suppressing tau neuropathology, restoring mitochondrial function, and alleviating neuroinflammation, thus inducing cognitive improvements in mouse models of AD. These findings highlight a potential strategy for brain\u2010targeted drug delivery in the management of the complex pathologies of AD.<\/jats:p>","DOI":"10.1002\/adma.202307081","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T18:40:17Z","timestamp":1708713617000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Customized Intranasal Hydrogel Delivering Methylene Blue Ameliorates Cognitive Dysfunction against Alzheimer's Disease"],"prefix":"10.1002","volume":"36","author":[{"given":"Yujing","family":"Liu","sequence":"first","affiliation":[{"name":"Science and Technology Innovation Center Guangzhou University of Chinese Medicine  Guangzhou 510405 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Tan","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Micro &amp; Nano Materials Interface Science College of 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